Significant gender differences in clinical disease activity and severity of multiple sclerosis: a Danish nationwide cohort study
Melinda Magyari1,2, Nils Koch-Henriksen1
1The Danish Multiple Sclerosis Registry, University Hospital Copenhagen, Rigshospitalet, 2Danish Multiple Sclerosis Center, University Hospital Copenhagen, Rigshospitalet, Denmark

To analyze the gender differences in disease activity in terms of frequency of relapses and development of disability in terms of time to certain disability milestones in a virtually complete nationwide cohort of patients with multiple sclerosis (MS) over 25 years.

The incidence of MS is significantly higher in women than in men, and several large epidemiological surveys have shown an increasing female to male sex ratio. In addition to this gender imbalance, some studies have indicated that MS evolves differently in men and women.

All Danish citizens with onset of relapsing-onset MS since 1996 who have undergone disease modifying treatment, have been followed at all Danish departments of neurology with biannually or annually visits with assessment of disability in terms of Expanded Disability Status Scale score and recording of number of relapses. Notification of The Danish MS Registry with these data is mandatory as part of a quality assessment program of the health authorities. Data were analyzed by Generalized Linear Models after weighting based on propensity scores for being female given all other demographic and clinical baseline variables. Time to endpoints were analyzed by weighted Cox regression.

We included 8922 patients, 2780 men and 6142 women who had been observed for a mean of 8.57 years (IQR 4.08-12.22). Annualized rates of breakthrough relapses were for men 0.186 and for women 0.225; p < 0.001. With women as reference the hazard ratios in men for reaching EDSS 4 and 6 were 1.39 (p<0.001) and 1.49 (p<0.001), respectively.

This follow-up study, complete from onset, gave strong evidence for more inflammatory disease activity in women particularly with younger age, and more neurodegeneration in men with shorter time to serious disability.